Carbocisteine 375mg capsules

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

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Active ingredient:
Carbocisteine
Available from:
Creo Pharma Ltd
ATC code:
R05CB03
INN (International Name):
Carbocisteine
Dosage:
375mg
Pharmaceutical form:
Capsule
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 03070000; GTIN: 5060222601183

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Carbocisteine 375mg Capsules

Package leaflet: Information for the user

Read all of this leaflet carefully before you

start taking this medicine.

Keep this leaflet. You may need to read it

again.

If you have any further questions, ask your

doctor or pharmacist.

This medicine has been prescribed for you

only. Do not pass it on to others. It may

harm them, even if their symptoms are the

same as yours.

If you get any side effects, talk to your

doctor or pharmacist. This includes any

possible side effects not listed in this

leaflet. See section 4.

What is in this leaflet:

1

What Carbocisteine 375mg Capsules

are and what they are used for

2

What you need to know before you

take Carbocisteine 375mg Capsules

3

How to take Carbocisteine 375mg

Capsules

4

Possible side effects

5

How to store Carbocisteine 375mg

Capsules

6

Contents of the pack and other

information

1

What Carbocisteine 375mg Capsules

are and what they are used for

Carbocisteine 375mg Capsules are used to

help treat respiratory tract problems (problems

with the breathing passages) characterised

by too much sticky mucus, including chronic

obstructive airways disease (lung damage with

restricted airways).

Carbocisteine 375mg Capsules contain

carbocisteine which belongs to a group of

medicines called mucolytics which cause the

mucus to be less sticky and easier to cough up.

2

What you need to know before you

take Carbocisteine 375mg Capsules

Do not take Carbocisteine 375mg

Capsules if you:

are allergic to carbocisteine or any of the

other ingredients of this medicine (listed in

section 6)

have an active peptic (stomach) ulcer.

Warnings and precautions

Talk to your doctor if you:

are elderly

have a history of stomach ulcers

are taking medicines that may cause

intestinal bleeding

are pregnant or planning to become

pregnant

are breast feeding.

Other medicines and Carbocisteine

375mg Capsules

Tell your doctor or pharmacist if you are taking,

have recently taken or might take any other

medicines, including medicines obtained

without a prescription. Currently carbocisteine

is not known to effect or be affected by any

other medicines you may be taking.

Pregnancy and breast-feeding

Carbocisteine 375mg Capsules are not

recommended during the first three months of

pregnancy.

If you are pregnant or breastfeeding, think you

may be pregnant or are planning to have a

baby ask your doctor for advice before taking

this medicine.

Driving and using machines

Carbocisteine 375mg Capsules are not

known to affect the ability to drive or operate

machinery.

3

How to take Carbocisteine 375mg

Capsules

Always take this medicine exactly as your

doctor has told you. Check with your doctor or

pharmacist if you are not sure.

The recommended adult dose at the beginning

of treatment is 2 capsules to be swallowed 3

times a day until a satisfactory improvement is

seen. The dose is then reduced to 1 capsule 4

times a day.

Use in children and adolecents

Other forms of this medicine may be more

suitable for children. Ask your doctor or

pharmacist.

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If you take more Carbocisteine 375mg

Capsules than you should

If you take too many capsules contact your

nearest hospital casualty department or tell

your doctor IMMEDIATELY. Take the carton

and this leaflet with you. If you take too many

Carbocisteine 375mg Capsules, it is likely

that you will get an upset stomach (stomach

disturbances).

If you forget to take Carbocisteine

375mg Capsules

Take the missed dose as soon as you remember.

If it is almost time for your next dose, do not

take the missed dose but simply take your next

dose at the normal time. Do not take a double

dose to make up for a forgotten dose.

If you stop taking Carbocisteine 375mg

Capsules

Talk to your doctor or pharmacist before

stopping this medicine.

If you have to go to the doctor, dentist or

hospital for any reason, tell them you are taking

Carbocisteine 375mg Capsules.

If you have any further questions on the use of

this product, ask your doctor or pharmacist.

4

Possible side effects

Like all medicines, this medicine can cause side

effects, although not everybody gets them.

A few people can be allergic to some

medicines:

Contact your doctor or go to the nearest

hospital casualty department IMMEDIATELY

if any of the following happen after taking

your medicine:

Wheezing, difficulty breathing or swallowing,

dizziness

Swelling of the eyelids, face, lips, tongue or

throat

Itchy skin rash affecting the whole body

You have blistering or bleeding of the skin,

including around your lips, eyes, mouth,

nose and genital. You may also have flu-like

symptoms and fever. This may be something

called ‘Stevens-Johnson’ syndrome.

Tell your doctor if you experience any of the

following:

Rare (may affect 1 in 1,000 people)

Skin rashes

Bleeding from the stomach or intestine (which

may be seen as black, tar-like stools).

Not known (frequency cannot be estimated

from the available data)

Being sick.

Reporting of side effects

If you get any side effects, talk to your doctor

or pharmacist. This includes any possible side

effects not listed in this leaflet. You can also

report side effects directly via Yellow Card

Scheme Website: www.mhra.gov.uk/yellowcard

By reporting side affects you can help provide

more information on the safety of this

medicine.

5

How to store Carbocisteine 375mg

Capsules

Keep out of the sight and reach of children.

Store below 25ºC.

Do not use this medicine after the expiry date

which is stated on the carton. The expiry date

refers to the last day of that month.

Do not throw away any medicines via

wastewater or household waste. Ask your

pharmacist how to throw away medicines you

no longer use. These measures will help protect

the environment.

6

Contents of the pack and other

information

What Carbocisteine 375mg Capsule

contains:

The active substance: carbocisteine 375mg

Other ingredients: microcrystalline cellulose,

macrogol, magnesium stearate

The capsules are made from gelatin, iron

yellow oxide (E172), brilliant blue FCF (E133)

and titanium dioxide (E171).

What Carbocisteine 375mg Capsules

look like and contents of the pack

Carbocisteine 375mg Capsules are yellow and

blue containing white to off-white odourless

powder.

The capsules are packed in blisters, in cartons

containing 120 capsules.

Marketing Authorisation Holder

Accord Healthcare Limited,

Sage House, 319 Pinner Road,

North Harrow, Middlesex,

HA1 4HF, United Kingdom

Manufacturer

Accord, Barnstaple, EX32 8NS, UK

This leaflet was last revised in March 2019

Accord Healthcare Ltd, North Harrow, HA1 4HF, UK

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Origination Date:

Revision Date:

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Supplier:

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Carbocisteine 375 mg Capsules, Hard

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 375 mg carbocisteine

Excipient(s) with known effect

Each Carbocisteine 375 mg Hard Capsule contains 22.5 mg lactose

monohydrate.

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Capsule, hard

Yellow cap and yellow body, size ‘0’ hard gelatine capsule, filled with white

to off white granular powder imprinted with C on cap and 375 on body.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Carbocisteine is a mucolytic agent for the adjunctive therapy of respiratory

tract disorders characterised by excessive, viscous mucus, including chronic

obstructive airways disease.

4.2

Posology and method of administration

Posology

Adults and elderly

Dosage is based upon an initial daily dosage of 2250 mg carbocisteine in divided

doses, reducing to 1500 mg daily in divided doses when a satisfactory response is

obtained e.g. two capsules three times a day reducing to one capsule four times a day.

Paediatric population

Carbocisteine 375 mg Capsules, hard are not recommended for children.

Method of administration

For oral use.

4.3

Contraindications

This medicine is contraindicated in case of:

Hypersensitivity to the active substance or to any of the excipients

listed in section 6.1.

Use in patients with active peptic ulceration.

4.4

Special warnings and precautions for use

Caution is recommended in the elderly, in those with a history of

gastroduodenal ulcers, or those taking concomitant medications known to cause

gastrointestinal bleeding. If gastrointestinal bleeding occurs, patients should

discontinue medication.

Patients with rare hereditary problems of galactose intolerance, the Lapp

lactase deficiency or glucose-galactose malabsorption should not take this

medicine.

4.5

Interaction with other medicinal products and other forms of interaction

None stated.

4.6

Fertility, pregnancy and lactation

Pregnancy

Although tests in mammalian species have revealed no teratogenic effects,

carbocisteine is not recommended during the pregnancy unless considered

essential by the physician.

Breast-feeding

It is unknown whether carbocisteine and / or its metabolites are excreted in

human milk.

A risk to the new born or infant cannot be excluded.

decision

must

made

whether

discontinue

breast-feeding

discontinue/abstain from carbocisteine therapy taking into account the benefit

of breast feeding for the child and the benefit of therapy for the woman.

Fertility

There is no consistent evidence on the effects of this product on fertility in

males or females.

4.7

Effects on ability to drive and use machines

None stated.

4.8

Undesirable effects

The following CIOMS frequency rating is used, when applicable: Very

common (

1/10); common (

1/100 to < 1/10); uncommon (

1/1,000 to <

1/100); rare (

1/10,000 to < 1/1,000); very rare (

1/10,000); not known

(cannot be estimated from the available data).

Immune System Disorders

There have been reports of anaphylactic reactions and fixed drug eruption.

Gastrointestinal disorders

There have been reports of gastrointestinal bleeding occurring during

treatment with carbocisteine, however the frequency is not known. Vomiting

has also been observed, though the frequency of this occurrence is not

known.

Skin and subcutaneous tissue disorders

There have been reports of skin rashes and allergic skin eruptions. Isolated

cases of bullous dermatitis such as Stevens–Johnson syndrome and erythema

multiforme have also been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal

product is important. It allows continued monitoring of the benefit/risk

balance of the medicinal product. Healthcare professionals are asked to

report any suspected adverse reactions via the Yellow Card Scheme at

www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the

Google Play or Apple App Store.

HPRA Pharmacovigilance Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

E-mail: medsafety@hpra.ie

4.9

Overdose

Gastric lavage may be beneficial, followed by observation. Gastrointestinal

disturbance is the most likely symptom of Carbocisteine overdosage.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Mucolytic, ATC code: R05CB03

Carbocisteine (S-carboxymethyl L-cysteine) has been shown in normal and bronchitic

animal models to affect the nature and amount of mucus glycoprotein which is

secreted by the respiratory tract. An increase in the acid: neutral glycoprotein ratio of

the mucus and a transformation of serous cells to mucus cells is known to be the

initial response to irritation and will normally be followed by hypersecretion. The

administration of Carbocisteine to animals exposed to irritants indicates that the

glycoprotein that is secreted remains normal; administration after exposure indicates

that return to the normal state is accelerated. Studies in humans have demonstrated

that Carbocisteine reduces goblet cell hyperplasia. Carbocisteine can therefore be

demonstrated to have a role in the management of disorders characterised by

abnormal mucus.

5.2

Pharmacokinetic properties

Carbocisteine is rapidly absorbed from the GI tract. In an 'in-house' study, at

steady state (7 days) Carbocisteine capsules 375 mg given as 2 capsules 3

times a day to healthy volunteers gave the following pharmacokinetic

parameters:

Plasma Determinations Mean

Range

(Hr) 2.0 1.0 - 3.0

T½ (Hr) 1.87 1.4 - 2.5

0.387

0.28 - 0.50

0-7.5

(mcg.Hr.ml

) 39.26 26.0 - 62.4

Derived Pharmacokinetic Parameters

(L.Hr

) 20.2

(ml.min

) 331

(L) 105.2

(L.Kg

1/75

*Calculated from dose for day 7 of study

5.3

Preclinical safety data

There are no preclinical data of relevance to the prescriber, which are

additional to those already included in other sections of the SmPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Capsule Content:

Lactose monohydrate

Povidone

Sodium lauril sulfate

Magnesium stearate

Capsule shell

Gelatin

Iron oxide yellow

titanium dioxide (E171).

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

2 years

6.4

Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container

The capsules are packaged in clear or opaque Alu-PVC blister packs.

Blister packs of 6, 18, 30 or 120 capsules.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in

accordance with local requirements.

7

MARKETING AUTHORISATION HOLDER

Key Pharmaceuticals Ltd.

Galen House, 83 High Street,

Somersham, Cambridgeshire

PE28 3JB. UK

8

MARKETING AUTHORISATION NUMBER(S)

PL 34424/0048

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

18/02/2020

10

DATE OF REVISION OF THE TEXT

18/02/2020

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CARBOCISTEINE 375MG CAPSULES

(Carbocisteine)

PL 18909/0364

UKPAR

TABLE OF CONTENTS

Lay Summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

Page 13

Steps taken after authorisation – summary

Page 14

Summary of Product Characteristics

Page 15

Product Information Leaflet

Page 20

Labelling

Page 26

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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CARBOCISTEINE 375MG CAPSULES

PL 18909/0364

LAY SUMMARY

The MHRA granted Arrow Generics Limited a Marketing Authorisation (licence) for the

medicinal product Carbocisteine 375mg Capsules (PL 18909/0364) on 02 March 2011.

This product is available as a prescription-only medicine (POM) and is used to help treat

respiratory tract problems (problems with the breathing passages) characterised by too

much sticky mucus, including chronic obstructive airways disease (lung damage with

restricted airways).

Carbocisteine 375mg Capsules contain carbocisteine which belongs to a group of

medicines called mucolytics which cause the mucus to be less sticky and easier to cough

No new or unexpected safety concerns arose from this application and it was, therefore,

judged that the benefits of taking Carbocisteine 375mg Capsules outweigh the risks; hence

a Marketing Authorisation has been granted.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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CARBOCISTEINE 375MG CAPSULES

PL 18909/0364

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 4

Pharmaceutical assessment

Page 6

Non-clinical assessment

Page 9

Clinical assessment

Page 10

Overall conclusions and risk benefit assessment

Page 12

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the MHRA granted Arrow

Generics Limited, a Marketing Authorisation for the medicinal product Carbocisteine

375mg Capsules (PL 18909/0364) on 02 March 2011. This product is available as a

prescription-only medicine (POM) and is indicated for the adjunctive therapy of respiratory

tract disorders characterised by excessive, viscous mucus, including chronic obstructive

airways disease.

This is an abridged application submitted under Article 10(1) of Directive 2001/83/EC, as

amended claiming to be a generic medicinal product of Mucodyne Capsules 375 mg

(Sanofi-Aventis, UK), which was first authorised in March 1992.

This product contains the active ingredient carbocisteine which belongs to a

pharmacotherapeutic group of drugs called mucolytic agents (ATC code: R05C B03).

Carbocisteine (5-carboxymethyl L-cysteine) has been shown in normal and bronchitic

animal models to affect the nature and amount of mucus glycoprotein that is secreted by the

respiratory tract. An increase in the acid:neutral glycoprotein ratio of the mucus and a

transformation of serous cells to mucus cells is known to be the initial response to irritation

and will normally be followed by hypersecretion. The administration of carbocisteine to

animals exposed to irritants indicates that the glycoprotein secreted remains normal;

administration after exposure indicates that return to the normal state is accelerated. Studies

in humans have demonstrated that carbocisteine reduces goblet cell hyperplasia.

Carbocisteine can therefore play a role in the management of disorders characterised by

abnormal mucus.

No new non-clinical data have been submitted, which is acceptable given that the

application was based on being a generic medicinal product of an originator product that

has been in clinical use for over 10 years.

A single-dose, bioequivalence study was submitted to support this application, comparing

the test product Carbocisteine 375mg Capsules (Arrow Generics Limited, UK) and the

reference product

Mucodyne 375 mg Capsules

(Aventis Pharma, UK). The bioequivalence

study was carried out in accordance with Good Clinical Practice (GCP).

With the exception of the bioequivalence study, no new clinical studies were performed,

which is acceptable given that the application was based on being a generic medicinal

product of an originator product that has been in clinical use for over 10 years.

The MHRA considers that the Pharmacovigilance System as described by the applicant

fulfils the requirements and provides adequate evidence that the applicant has the services

of a qualified person responsible for pharmacovigilance and has the necessary means for

the notification of any adverse reaction suspected of occurring either in the Community or

in a third country. A suitable justification has been provided for the non-submission of a

Risk Management Plan.

No new or unexpected safety concerns were raised during the assessment of this

application and it was, therefore, judged that the benefits of taking Carbocisteine 375mg

Capsules outweigh the risks; hence a Marketing Authorisation has been granted.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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PHARMACEUTICAL ASSESSMENT

ACTIVE SUBSTANCE

INN:

Carbocisteine

Chemical names:

(Carboxymethyl)thio- 3 –alanine Amine-2-(carboxymethyl)thio-3-

propionic acid S- carboxymethyl – L – cisteine (R) – 2 – amino – 3 –

[ carboxymethyl) thio] propionic acid

Structure:

Molecular formula:

Molecular weight:

179.2

Description:

White crystalline powder

Solubility:

Carbocisteine is practically insoluble in water, in alcohol and in

ether. It dissolves in diluted mineral acids and in diluted solutions of

alkali hydroxides.

Carbocisteine is the subject of a European Pharmacopoeia monograph.

All aspects of the manufacture and control of the active substance carbocisteine are covered

by a European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability.

Suitable specifications have been provided for all packaging used. The primary packaging

has been shown to comply with current guidelines concerning contact with food.

Appropriate stability data have been generated to support a suitable retest period when

stored in the proposed packaging.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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MEDICINAL PRODUCT

Other ingredients

Other ingredients consist of pharmaceutical excipients, namely microcrystalline cellulose,

macrogol, magnesium stearate, gelatin, titanium dioxide (E171), Iron Yellow Oxide (body,

E172) and Brilliant Blue FCF (cap, E133).

Appropriate justification for the inclusion of each excipient has been provided.

All excipients used comply with their respective European Pharmacopoeia monograph.

Satisfactory Certificates of Analysis have been provided for all excipients.

With the exception of gelatin, none of the excipients are of animal or human origin. The

suppliers of gelatin have provided European Directorate for the Quality of Medicines

(EDQM) Certificates of Suitability, which covers all aspects of the manufacture and control

of the excipient. No genetically modified organisms (GMO) have been used in the

preparation of these excipients.

Pharmaceutical development

The aim of the development programme was to formulate a safe, efficacious, stable product

that could be considered a generic medicinal product of

Mucodyne 375 mg Capsules

(Aventis

Pharma, UK)

Suitable data on the quality critical attributes of the product have been provided for this

application.

Comparable

in vitro

dissolution and impurity profiles have been provided for the proposed

and originator product.

Manufacture

A description and flow-chart of the manufacturing method has been provided.

Satisfactory batch formulae have been provided for the manufacture of the product, along

with an appropriate account of the manufacturing process. The manufacturing process has

been validated and has shown satisfactory results.

Finished product specification

The finished product specification is satisfactory. Test methods have been described and

have been adequately validated, as appropriate. Batch data have been provided and comply

with the release specification. Certificates of Analysis have been provided for any working

standards used.

Container Closure System

The product is packaged in polyvinylchloride / aluminium blisters in pack sizes of 20, 30,

60, 100 and 120 capsules

It has been stated that not all pack sizes may be marketed, however, the marketing

authorisation holder has committed to submit the mock-ups to the relevant regulatory

authorities for approval before marketing.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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Stability

Finished product stability studies have been conducted in accordance with current

guidelines and results were within the proposed specification limits. Based on the results, a

shelf-life of 5 years with the special storage conditions ‘Store below 25ºC.’

Bioequivalence/Bioavailability

Satisfactory Certificates of Analysis have been provided for the test and reference batches

used in the bioequivalence study.

Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and

Labelling

The SPC, PIL and labelling are pharmaceutically satisfactory.

A package leaflet has been submitted to the MHRA along with results of consultations with

target patient groups ("user testing"), in accordance with Article 59 of Council Directive

2001/83/EC, as amended. The results indicate that the package leaflet is well-structured

and organised, easy to understand and written in a comprehensive manner. The test shows

that the patients/users are able to act upon the information that it contains.

MAA Form

The MAA form is pharmaceutically satisfactory.

Expert Report

A pharmaceutical expert report has been written by an appropriately qualified person and is

a suitable summary of the pharmaceutical aspects of the dossier.

Conclusion

It is recommended that a marketing authorisation is granted for this application.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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NON-CLINICAL ASSESSMENT

PHARMACODYNAMICS, PHARMACOKINETICS AND TOXICOLOGY

No new non-clinical data were submitted, which is acceptable given that the proposed

product is a generic medicinal product of an originator product that has been licensed for

over 10 years.

NON-CLINICAL EXPERT REPORT

The non-clinical expert report has been written by an appropriately qualified person and is

a suitable summary of the non-clinical aspects of the dossier.

ENVIRONMENTAL RISK ASSESSMENT

A suitable justification has been provided for non-submission of an Environmental Risk

Assessment. As this product is intended for generic substitution with a product that is

already marketed, no increase in environmental burden is anticipated. Thus, the

justification for non-submission of an Environmental Risk Assessment is accepted.

CONCLUSION

It is recommended that a marketing authorisation is granted for this application.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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CLINICAL ASSESSMENT

CLINICAL PHARMACOLOGY

The clinical pharmacology of carbocisteine is well-known. With the exception of the

bioequivalence study, no pharmacokinetic or pharmacodynamic data were submitted for

this application, and none were required for an application of this type.

The following bioequivalence study was submitted:

An open-label, randomised, two-way, two-period, single dose crossover study,

comparing the pharmacokinetics of the test product Carbocisteine 375mg Capsules

(Arrow Generics Limited, UK) versus the reference product

Mucodyne 375 mg

Capsules

(Aventis Pharma, UK) in healthy adult male volunteers under fasting

conditions.

Subjects

were administered a single oral dose of 2 x 375mg carbocisteine of the test or the

reference product

after an overnight fast of at least 10 hours. Blood samples were collected

pre- and up to 12 hours post dose. Meals were provided at 4, 8 and 12 hours post dose. The

treatment phases were separated by a washout period of at least 7 days

The main pharmacokinetic results for carbocisteine are presented below (geometric means,

ratio and confidence intervals [CI]):

Treatment

AUC

0-t

(ng.h/ml)

AUC

0-∞

(ng.h/ml)

C

max

(ng/ml)

Test *

20363.05

21165.17

5809.40

Reference *

20632.12

21798.04

5420.21

Ratio (90% CI)

97.30

(91.24-103.76)

95.77

(90.03-101.88)

106.05

(99.50-113.05)

AUC

0-∞

area under the plasma concentration-time curve from time zero to infinity

AUC

0-t

area under the plasma concentration-time curve from time zero to t hours

C

max

maximum plasma concentration

90 % Confidence Interval calculated using log-transformed data

The current

Guidance on the Investigation of Bioequivalence

(CPMP/EWP/QWP/1041/98

Rev 1) defines the confidence limits as 80% to 125% for C

and AUC values. The 90%

confidence intervals of the test/reference ratio for the log-transformed parameters C

and AUC

0-∞

lie within acceptable limits. Thus the data support the claim that the

test product Carbocisteine 375mg Capsules (Arrow Generics Limited, UK) is bioequivalent

to the reference product

Mucodyne 375 mg Capsules

(Aventis Pharma, UK).

EFFICACY

No new efficacy data have been submitted and none are required for an application of this

type.

SAFETY

No new safety concerns were highlighted during the pharmacokinetic study.

EXPERT REPORT

A clinical expert report has been written by an appropriately qualified person and is a

suitable summary of the clinical aspects of the dossier.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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PRODUCT INFORMATION:

Summary of Product Characteristics (SmPC)

The SmPC is clinically satisfactory and is consistent with that for the reference product.

Patient Information Leaflet (PIL)

The PIL is satisfactory and consistent with the SmPC.

Labelling

The labelling is satisfactory.

CONCLUSION

The applicant has demonstrated that this product and its reference product are

bioequivalent. It is recommended that a marketing authorisation is granted for this

application.

MHRA PAR – Carbocisteine 375mg Capsules (PL 18909/0364)

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